基于生物信息学探讨佛山市中医院骨九方治疗骨关节炎的分子机制OA

Objective To investigate the molecular mechanism of Foshan Hospital of Traditional Chinese Medicine Bone Formula IX in treating osteoarthritis(OA)based on bioinformatics.Methods Potential active components and corresponding targets of Bone Formula IX were collected from the TCMSP and HERB databases.OA-related microarray datasets were obtained from the GEO database,and Weighted Gene Co-expression Network Analysis(WGCNA)and differential expression analysis were performed to identify OA-related module genes and differentially expressed genes.The integrated bioinformatics datasets were subjected to functional enrichment analysis.Protein-protein interaction(PPI)network analysis was conducted,and four machine learning methods(RF,SVM,XGBoost,GLM)were employed to identify key genes of Bone Formula IX for OA treatment.Expression analysis and single-sample Gene Set Enrichment Analysis(GSEA)of the key genes were performed.Finally,molecular docking simulations were used to validate the key active components and targets.Results A total of 660 potential active components in Bone Formula IX and 447 potential targets were identified,along with 2 OA-related WGCNA modules and 1 546 upregulated differentially expressed genes in OA.Forty-seven overlapping targets were found between Bone Formula IX and OA.Functional enrichment analysis revealed associations with the TNF signaling pathway,NF-kappa B signaling pathway,Hippo signaling pathway,PI3K-Akt signaling pathway,JAK-STAT signaling pathway,and p53 signaling pathway,among others.The RF and SVM machine learning models demonstrated good predictive performance.Combined with PPI analysis,β-actin(ACTB)was identified as a key gene for Bone Formula IX in treating OA.Finally,molecular docking results indicated that key components such as kaempferol,genistein,luteolin,and wogonin exhibited strong binding affinity with the key target.Conclusion Bone Formula IX acts through multiple components,targets,and pathways to inhibit OA inflammatory levels,suppress chondrocyte apoptosis and reduce cartilage degradation,and regulate the proliferation and differentiation of osteoblasts and osteoclasts to alleviate bone loss.This study provides a theoretical basis for further clinical research and pharmacological studies on Bone Formula IX for OA treatment.